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Self-consistent field convergence for proteins: a comparison of full and localized-molecular-orbital schemes

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Abstract

Proteins in the gas phase present an extreme (and unrealistic) challenge for self-consistent-field iteration schemes because their ionized groups are very strong electron donors or acceptors, depending on their formal charge. This means that gas-phase proteins have a very small band gap but that their frontier orbitals are localized compared to “normal” conjugated semiconductors. The frontier orbitals are thus likely to be separated in space so that they are close to, but not quite, orthogonal during the SCF iterations. We report full SCF calculations using the massively parallel EMPIRE code and linear scaling localized-molecular-orbital (LMO) calculations using Mopac2009. The LMO procedure can lead to artificially over-polarized wavefunctions in gas-phase proteins. The full SCF iteration procedure can be very slow to converge because many cycles are needed to overcome the over-polarization by inductive charge shifts. Example molecules have been constructed to demonstrate this behavior. The two approaches give identical results if solvent effects are included.

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References

  1. Clark T, Stewart JJP (2011) MNDO-like semiempirical molecular orbital theory and its application to large systems. In: Reimers JJ (ed) Computational methods for large systems, chap 8. Wiley, Chichester,

  2. Yang W (1991) Direct calculation of electron density in density-functional theory. Phys Rev Lett 66:1438–1441

    Article  CAS  Google Scholar 

  3. Dixon SL, Merz KM Jr (1997) Fast, accurate semiempirical molecular orbital calculations for macromolecules. J Chem Phys 107:879–893

    Article  CAS  Google Scholar 

  4. Ababoua A, van der Vaart A, Gogonea V, Merz KM Jr (2007) Interaction energy decomposition in protein-protein association: a quantum mechanical study of barnase-barstar complex. Biophys Chem 125:221–236

    Article  CAS  Google Scholar 

  5. Stewart JJP (1996) Application of localized molecular orbitals to the solution of semiempirical self-consistent field equations. Int J Quantum Chem 58:133–146

    Article  CAS  Google Scholar 

  6. Stewart JJP (2009) Application of the PM6 method to modeling proteins. J Mol Model 15:765–805

    Article  CAS  Google Scholar 

  7. Hennemann M, Clark T (2013) EMPIRE. Universität Erlangen-Nürnberg and Cepos InSilico Ltd (http://www.ceposinsilico.de/products/empire.htm). Accessed 19 Jan 2014

  8. Stewart JJP (2008) MOPAC2009. Stewart Computational Chemistry, Colorado Springs, CO, USA. http://OpenMOPAC.net. Accessed 19 Jan 2014

  9. Dewar MJS, Zoebisch EG, Healy EF, Stewart JJP (1985) Development and use of quantum mechanical molecular models. 76. AM1: a new general purpose quantum mechanical molecular model. J Am Chem Soc 107:3902–3909

    Article  CAS  Google Scholar 

  10. Stewart JJP, Császár P, Pulay P (1982) Fast semiempirical calculations. J Comput Chem 3:227–228

    Article  CAS  Google Scholar 

  11. Min JR, Schuetz A, Loppnau P, Weigelt J, Sundstrom M, Arrowsmith CH, Edwards AM, Bochkarev A, Plotnikov AN (2014) Human NR4A1 ligand-binding domain. http://www.pdb.org/pdb/explore/explore.do?structureId=2QW4. Accessed 19 Jan 2014

  12. Case DA, Darden TA, Cheatham III TE, Simmerling CL, Wang J, Duke RE, Luo R, Walker RC, Zhang W, Merz KM, Roberts B, Hayik S, Roitberg A, Seabra G, Swails J, Goetz AW, Kolossváry I, Wong KF, Paesani F, Vanicek J, Wolf RM, Liu J, Wu X, Brozell SR, Steinbrecher T, Gohlke H, Cai Q, Ye X, Wang J, Hsieh M-J, Cui G, Roe DR, Mathews DH, Seetin MG, Salomon-Ferrer R, Sagui C, Babin V, Luchko T, Gusarov S, Kovalenko A, Kollman PA (2012) AMBER 12. University of California, San Francisco. http://ambermd.org/. Accessed 19 Jan 2014

  13. Horn HW, Swope WC, Pitera JD, Madura JD, Dick TJ, Hura GL, Head-Gordon T (2004) Development of an improved four-site water model for biomolecular simulations: TIP4P−Ew. J Chem Phys 120:9665–9678

    Article  CAS  Google Scholar 

  14. Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, Simmerling C (2006) Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins 65:712–725

    Article  CAS  Google Scholar 

  15. Darden T, York D, Pederson L (1993) Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems. J Chem Phys 98:10089–10092

    Article  CAS  Google Scholar 

  16. Yoneya M, Berendsen HJC, Hirasawa K (1994) A noniterative matrix method for constraint molecular-dynamics simulations. Mol Simul 13:395–405

    Article  CAS  Google Scholar 

  17. Ehresmann B, Martin B, Horn AHC, Clark T (2003) Local molecular properties and their use in predicting reactivity. J Mol Model 9:342–347

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft as part of the Excellence Cluster Engineering of Advanced Materials and by the Bundesministerium für Bildung und Forschung as part of the high-performance Computer-Aided Drug Design (hpCADD) project.

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Authors and Affiliations

  1. Computer-Chemie-Centrum and Interdisciplinary Center for Molecular Materials, Department Chemie und Pharmazie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nägelsbachstrasse 25, 91052, Erlangen, Germany

    Christian R. Wick, Matthias Hennemann & Timothy Clark

  2. Stewart Computational Chemistry, 15210 Paddington Circle, Colorado Springs, CO, 80921-2512, USA

    James J. P. Stewart

  3. Centre for Molecular Design, University of Portsmouth, King Henry Building, King Henry I Street, Portsmouth, PO1 2DY, UK

    Timothy Clark

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  1. Christian R. Wick
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  2. Matthias Hennemann
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  3. James J. P. Stewart
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  4. Timothy Clark
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Corresponding author

Correspondence to Timothy Clark.

Electronic supplementary material

The molecular structures used for hNur77 and 3 (.xyz) files are available as electronic Supporting information.

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(XYZ 290 kb)

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Wick, C.R., Hennemann, M., Stewart, J.J.P. et al. Self-consistent field convergence for proteins: a comparison of full and localized-molecular-orbital schemes. J Mol Model 20, 2159 (2014). https://doi.org/10.1007/s00894-014-2159-y

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  • DOI: https://doi.org/10.1007/s00894-014-2159-y

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